Identification of a Bromodomain-like region in 15-Lipoxygenase-1 explains its Nuclear Localization

Deng Chen, Zhangping Xiao, Hao Guo, Dea Gogishvili, Rita Setroikromo, Petra E van der Wouden, Frank J Dekker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Lipoxygenase (LOX) activity provides oxidative lipid metabolites, which are involved in inflammatory disorders and tumorigenesis. Activity-based probes to detect the activity of LOX enzymes in their cellular context provide opportunities to explore LOX biology and LOX inhibition. Here, we developed Labelox B as a potent covalent LOX inhibitor for one-step activity-based labelling of proteins with LOXs activity. Labelox B was used to establish an ELISA-based assay for affinity capture and antibody-based detection of specific LOX isoenzymes. Moreover, Labelox B enabled efficient activity-based labeling of endogenous LOXs in living cells. LOX proved to localize in the nucleus, which was rationalized by identification of a functional bromodomain-like consensus motif in 15-LOX-1. This indicates that 15-LOX-1 is not only involved in oxidative lipid metabolism, but also in chromatin binding, which suggests a potential role in chromatin modifications.

Original languageEnglish
Pages (from-to)21875-21883
Number of pages21875
JournalAngewandte Chemie (International ed. in English)
Volume60
Issue number40
Early online date13-Aug-2021
DOIs
Publication statusPublished - 27-Sep-2021

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